Prognostic Indicators in Pediatric Clinically Isolated Syndrome

Pietro Iaffaldano; Marta Simone; Giuseppe Lucisano; Angelo Ghezzi; Gabriella Coniglio; Vincenzo Brescia Morra; Giuseppe Salemi; Francesco Patti; Alessandra Lugaresi; Guillermo Izquierdo; Roberto Bergamaschi; Jose Antonio Cabrera-Gomez; Carlo Pozzilli; Enrico Millefiorini; Raed Alroughani; Cavit Boz; Eugenio Pucci; Giovanni Bosco Zimatore; Patrizia Sola; Giacomo Lus; Davide Maimone; Carlo Avolio; Eleonora Cocco; Seyed Aidin Sajedi; Gianfranco Costantino; Pierre Duquette; Vahid Shaygannejad; Thor Petersen; Ricardo Fernandez Bolanos; Damiano Paolicelli; Carla Tortorella; Tim Spelman; Lucia Margari; Maria Pia Amato; Giancarlo Comi; Helmut Butzkueven; Italian iMedWeb Registry & MSBase; Raymond Hupperts; Maria Trojano

doi:10.1002/ana.24938

Prognostic Indicators in Pediatric Clinically Isolated Syndrome

Pietro Iaffaldano, Marta Simone, Giuseppe Lucisano, Angelo Ghezzi, Gabriella Coniglio, Vincenzo Brescia Morra, Giuseppe Salemi, Francesco Patti, Alessandra Lugaresi, Guillermo Izquierdo, Roberto Bergamaschi, Jose Antonio Cabrera-Gomez, Carlo Pozzilli, Enrico Millefiorini, Raed Alroughani, Cavit Boz, Eugenio Pucci, Giovanni Bosco Zimatore, Patrizia Sola, Giacomo LusDavide Maimone, Carlo Avolio, Eleonora Cocco, Seyed Aidin Sajedi, Gianfranco Costantino, Pierre Duquette, Vahid Shaygannejad, Thor Petersen, Ricardo Fernandez Bolanos, Damiano Paolicelli, Carla Tortorella, Tim Spelman, Lucia Margari, Maria Pia Amato, Giancarlo Comi, Helmut Butzkueven, Italian iMedWeb Registry & MSBase, Raymond Hupperts, Maria Trojano^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients.

Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data.

Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening.

Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population.

Original language	English
Pages (from-to)	729-739
Number of pages	11
Journal	Annals of Neurology
Volume	81
Issue number	5
DOIs	https://doi.org/10.1002/ana.24938
Publication status	Published - May 2017

Keywords

ONSET MULTIPLE-SCLEROSIS
NATURAL-HISTORY
FOLLOW-UP
DISABILITY PROGRESSION
PARACLINICAL FEATURES
TRANSVERSE MYELITIS
INTERFERON BETA-1B
OPTIC NEURITIS
CHILDREN
CHILDHOOD

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10.1002/ana.24938

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Iaffaldano, P., Simone, M., Lucisano, G., Ghezzi, A., Coniglio, G., Morra, V. B., Salemi, G., Patti, F., Lugaresi, A., Izquierdo, G., Bergamaschi, R., Cabrera-Gomez, J. A., Pozzilli, C., Millefiorini, E., Alroughani, R., Boz, C., Pucci, E., Zimatore, G. B., Sola, P., ... Trojano, M. (2017). Prognostic Indicators in Pediatric Clinically Isolated Syndrome. Annals of Neurology, 81(5), 729-739. https://doi.org/10.1002/ana.24938

@article{baa38bbd78a141c6ad2ea6fd926dfd80,

title = "Prognostic Indicators in Pediatric Clinically Isolated Syndrome",

abstract = "Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients.Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data.Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening.Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population.",

keywords = "ONSET MULTIPLE-SCLEROSIS, NATURAL-HISTORY, FOLLOW-UP, DISABILITY PROGRESSION, PARACLINICAL FEATURES, TRANSVERSE MYELITIS, INTERFERON BETA-1B, OPTIC NEURITIS, CHILDREN, CHILDHOOD",

author = "Pietro Iaffaldano and Marta Simone and Giuseppe Lucisano and Angelo Ghezzi and Gabriella Coniglio and Morra, {Vincenzo Brescia} and Giuseppe Salemi and Francesco Patti and Alessandra Lugaresi and Guillermo Izquierdo and Roberto Bergamaschi and Cabrera-Gomez, {Jose Antonio} and Carlo Pozzilli and Enrico Millefiorini and Raed Alroughani and Cavit Boz and Eugenio Pucci and Zimatore, {Giovanni Bosco} and Patrizia Sola and Giacomo Lus and Davide Maimone and Carlo Avolio and Eleonora Cocco and Sajedi, {Seyed Aidin} and Gianfranco Costantino and Pierre Duquette and Vahid Shaygannejad and Thor Petersen and {Fernandez Bolanos}, Ricardo and Damiano Paolicelli and Carla Tortorella and Tim Spelman and Lucia Margari and Amato, {Maria Pia} and Giancarlo Comi and Helmut Butzkueven and {Italian iMedWeb Registry & MSBase} and Raymond Hupperts and Maria Trojano",

year = "2017",

month = may,

doi = "10.1002/ana.24938",

language = "English",

volume = "81",

pages = "729--739",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "Wiley",

number = "5",

}

Iaffaldano, P, Simone, M, Lucisano, G, Ghezzi, A, Coniglio, G, Morra, VB, Salemi, G, Patti, F, Lugaresi, A, Izquierdo, G, Bergamaschi, R, Cabrera-Gomez, JA, Pozzilli, C, Millefiorini, E, Alroughani, R, Boz, C, Pucci, E, Zimatore, GB, Sola, P, Lus, G, Maimone, D, Avolio, C, Cocco, E, Sajedi, SA, Costantino, G, Duquette, P, Shaygannejad, V, Petersen, T, Fernandez Bolanos, R, Paolicelli, D, Tortorella, C, Spelman, T, Margari, L, Amato, MP, Comi, G, Butzkueven, H, Italian iMedWeb Registry & MSBase, Hupperts, R & Trojano, M 2017, 'Prognostic Indicators in Pediatric Clinically Isolated Syndrome', Annals of Neurology, vol. 81, no. 5, pp. 729-739. https://doi.org/10.1002/ana.24938

TY - JOUR

T1 - Prognostic Indicators in Pediatric Clinically Isolated Syndrome

AU - Iaffaldano, Pietro

AU - Simone, Marta

AU - Lucisano, Giuseppe

AU - Ghezzi, Angelo

AU - Coniglio, Gabriella

AU - Morra, Vincenzo Brescia

AU - Salemi, Giuseppe

AU - Patti, Francesco

AU - Lugaresi, Alessandra

AU - Izquierdo, Guillermo

AU - Bergamaschi, Roberto

AU - Cabrera-Gomez, Jose Antonio

AU - Pozzilli, Carlo

AU - Millefiorini, Enrico

AU - Alroughani, Raed

AU - Boz, Cavit

AU - Pucci, Eugenio

AU - Zimatore, Giovanni Bosco

AU - Sola, Patrizia

AU - Lus, Giacomo

AU - Maimone, Davide

AU - Avolio, Carlo

AU - Cocco, Eleonora

AU - Sajedi, Seyed Aidin

AU - Costantino, Gianfranco

AU - Duquette, Pierre

AU - Shaygannejad, Vahid

AU - Petersen, Thor

AU - Fernandez Bolanos, Ricardo

AU - Paolicelli, Damiano

AU - Tortorella, Carla

AU - Spelman, Tim

AU - Margari, Lucia

AU - Amato, Maria Pia

AU - Comi, Giancarlo

AU - Butzkueven, Helmut

AU - Italian iMedWeb Registry & MSBase

AU - Hupperts, Raymond

AU - Trojano, Maria

PY - 2017/5

Y1 - 2017/5

N2 - Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients.Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data.Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening.Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population.

AB - Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients.Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data.Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening.Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population.

KW - ONSET MULTIPLE-SCLEROSIS

KW - NATURAL-HISTORY

KW - FOLLOW-UP

KW - DISABILITY PROGRESSION

KW - PARACLINICAL FEATURES

KW - TRANSVERSE MYELITIS

KW - INTERFERON BETA-1B

KW - OPTIC NEURITIS

KW - CHILDREN

KW - CHILDHOOD

U2 - 10.1002/ana.24938

DO - 10.1002/ana.24938

M3 - Article

SN - 0364-5134

VL - 81

SP - 729

EP - 739

JO - Annals of Neurology

JF - Annals of Neurology

IS - 5

ER -

Prognostic Indicators in Pediatric Clinically Isolated Syndrome

Abstract

Keywords

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